The arterial chemoreflex is activated during hypoxia by stimulation of chemoreceptors located in the carotid sinus and aortic arch. The reflex increase in respiratory drive and sympathetic and parasympathetic tone are important for homeostatic regulation of blood gases. Although the reflex actions associated with arterial chemoreceptor stimulation are well documented, the neural circuitry underlying the coordination and modulation of cardiorespiratory responses during chemoreceptor stimulation is not well defined. The primary objective of the present research proposal is to investigate the role of the lateral parabrachial nucleus (LPBN) in modulation of the arterial chemoreflex. Anatomical studies have demonstrated that the LPBN is reciprocally connected with both the nucleus tractus solitarius (NTS) and cardiorespiratory regions of the ventrolateral medulla (VLM). Activation of the LPBN has profound effects on both sympathetic drive and respiratory rate and recently a large percent of LPBN neurons have been shown to receive chemoreceptor inputs, suggesting that the LPBN may be an important nucleus in the central modulation of arterial chemoreflex responses. The proposed research will employ both reflex and single unit recording studies to investigate how connections between the LPBN, NTS and VLM interact to modulate cardiovascular and respiratory components of the arterial chemoreflex. The proposed studies will also focus on identifying possible functional differences between two subnuclei of the LPBN (dorsal lateral vs. external lateral) in modulation of arterial chemoreflex responses. Preliminary studies suggest that these two regions may have opposite effects on arterial chemoreflex regulation. The results of the proposed studies will increase our understanding of the role of the LPBN in cardiorespiratory regulation. This new information will also provide insights into the central circuits involved in modulating arterial chemoreflex responses and potentially may lead to an understanding of the central mechanisms underlying the hypothesized dysfunction of arterial chemoreflex responses in pathophysiological states such as hypertension and sleep apnea.